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Complex spikes (CSs) driven by inferior olivary neurons have crucial roles in motor control. Wang et al. identified an excitatory pathway from the cerebellar nuclei to the inferior olive that drives rapid feedback CSs and contributes to the fine control of ocular and body movements.
The authors derive a neural network theory of systems consolidation to assess why some memories consolidate more than others. They propose that brains regulate consolidation to optimize generalization, so only predictable memory components consolidate.
Chandelier cells organize neural coding and mediate learning by establishing inhibitory circuit motifs over individual pyramidal neurons and suppressing irrelevant activity via adaptive axo-axonic synaptic plasticity, subserving efficient computation.
The factors that regulate astrogenesis during development are not completely understood. Here the authors propose a data-driven framework to leverage transcriptomic data to identify ligand–receptor pairs promoting astrogenesis and validate their effects in human cortical organoids and fetal progenitor cells.
The cellular and molecular mechanisms underlying major depressive disorder are unclear. Here, the authors report cell type- and cortical layer-specific gene expression changes and identify one microglia subpopulation associated with depressive-like behavior in female non-human primates.
To understand how antipsychotics modulate neural activity in the striatum, Yun et al. used in vivo imaging and found a correlation between clinical efficacy and the modulation of D1R-expressing, rather than D2R-expressing, striatal neurons in mice.
Changing temperature in striatum warped neural activity in time and categorical time judgments in rats. Similar effects on movement were not observed. Striatal dynamics may thus support discrete decisions and not continuous motor control.
Using direct recordings from human MTL neurons during sleep, Staresina et al. reveal that neuronal firing and communication—thought to underlie synaptic plasticity and learning—are controlled by coupled slow oscillations, spindles and ripples.
Dridi et al. identified a mechanism for cognitive dysfunction after heart failure in which hyper-adrenergic signaling and transforming growth factor-beta activation induced Ca2+ leak by RyR2 channels in hippocampal neurons.
Myelin is widely believed to protect axons from damage in multiple sclerosis. The authors challenge this view and find that myelin insulation renders axons more vulnerable to degeneration in an autoimmune environment.
Global reduction of m6A leads to mRNA stabilization in ALS/FTD caused by C9ORF72 repeat expansion. m6A also regulates repeat RNA decay. Elevating m6A reduces RNA and dipeptide repeats, restores mRNA homeostasis and improves patient neuron survival.
Autism spectrum disorder (ASD) is characterized by heterogeneous phenotypes. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, the authors propose a framework to leverage multi-omic datasets and investigate how the GBA influences ASD.
The authors find a surprising diversity in hypothalamic neurons projecting to habenula, and using patch-sequencing (Patch-seq), identify an estrogen receptor-expressing neuron type that signals aversion and is linked to stress in female mice.
Oxycodone withdrawal triggered distinct transcriptomic changes in the ventral tegmental area, nucleus accumbens and medial prefrontal cortex in mice with and without chronic pain, with histone deacetylase 1 (HDAC1) as a common upstream regulator. A novel HDAC1/HDAC2 inhibitor reduced behavioral manifestations of oxycodone withdrawal.
Yin et al. identify miR-155–IFN-γ signaling that regulates a protective microglial subset in a mouse model of Alzheimer’s disease. These microglia enhance plaque compaction, reduce dystrophic neurites and synaptic degradation, and improve cognition.
Camacho et al. show that emotion concepts are represented throughout the brain, giving insight to how the brain perceives real-world emotions. These patterns are present before children enter school and become more standardized across adolescence.
Vasek et al. demonstrate that distal processes of microglia locally translate specific mRNAs including those related to immunity and phagocytosis. They then show that local protein synthesis is necessary for microglial process-initiated phagocytosis.
Moliner et al. show that psychedelics directly bind to the BDNF receptor TrkB with high affinity and promote BDNF-mediated plasticity and antidepressant-like effects, whereas their hallucinogenic-like effects are independent of TrkB binding.
Geva-Sagiv et al. performed real-time closed-loop intracranial stimulation in human sleep. Brief prefrontal pulses, precisely timed with MTL slow-wave active periods, led to correlated enhancements in sleep oscillation coupling and memory accuracy.
Holstein-Rønsbo et al. show that functional hyperemia increases glymphatic CSF inflow and clearance. Direct stimulation of vascular smooth muscle cells, in the absence of neuronal activation, similarly enhances glymphatic flow.